Patient death raises concerns over Roche haemophilia drug

Fresh safety concerns have emerged over Roche’s haemophilia drug, emicizumab, after a patient death on a late-stage trial.

The HAVEN 1 phase 3 trial reported positive results before Christmas, in patients 12 years of age and older with haemophilia A and inhibitors to factor VIII.

The announcement only provided top-line information, and a full analysis of the trial has yet to be published, so it is too early to make firm conclusions about the safety of the drug.

But there have already been worries over two patients who had developed thromboembolic events and thrombotic microangiopathy (TMA) – the restriction of blood flow in small capillaries, potentially damaging organs such as the kidneys and brain.

In the latest event, revealed in a letter to the European Haemophilia Consortium, Roche said there had been two new reports of serious adverse events in the study, in one case leading to a patient death.

Roche said that patient in question experienced a serious rectal haemorrhage and received bypassing agents, including repeated doses of activated prothrombin complex after which the patient developed signs of TMA.

The patient declined blood transfusions, and Roche said the investigators’ assessment is that the cause of death was the rectal haemorrhage, and was unrelated to emicizumab.

In its letter Roche stressed that patient safety is of “paramount importance”, adding that it was “deeply saddened” by the news.

Roche has high hopes for emicizumab, which if approved could generate sales of more than a billion dollars in a market dominated by Novo Nordisk and Shire.

A bispecific antibody, emicizumab was developed by Chugai, in which Roche holds a majority stake.

The drug is designed to bring together factors IXa and X, proteins required to activate the natural coagulation cascade and restore the blood clotting process.

Roche expects to file the drug to regulators in the haemophilia A without inhibitors this year

It is also developing the drug in haemophilia A without inhibitors, and plans filings in this use in 2018.